Is FDA Trial Design Scrutiny Increasing or Just Less Predictable?

In a recent video interview with Applied Clinical Trials, Meri Beckwith, Co-CEO, Lindus Health, discussed the evolving perception of breakthrough designation amid the FDA’s recent Complete Response Letters (CRLs) issued to Replimune and Capricor. He emphasized that breakthrough designation does not necessarily guarantee approval, but offers quicker decision access and investor signaling. Beckwith also stressed the importance of agility in trial design, advocating for adaptive trials and control groups where ethical. To mitigate regulatory unpredictability and avoid costly CRLs, he highlighted the need for future-proofing trial protocols with adaptive randomization and synthetic control groups.

ACT: Do you think the growing scrutiny around trial design is a sign of regulatory unpredictability, or are we seeing more transparent expectations from the FDA that just haven’t been operationalized effectively yet?

Beckwith: I’m not sureI'd quite say that there is more scrutiny, or there's a pattern of more scrutiny, on trial design. I do think in this case, it just seems to be kind of like a personally driven issue with a few kind of personalities inside the FDA. Having said that though, maybe over the next year or two, there's a pretty consistent pattern of the FDA rejecting more studies that aren't controlled or insisting on more robust results, more carefully scrutinizing sample sizes, those kinds of things, remains to be seen. My view is that these decisions, it's just kind of unpredictability, the result of one set of reviewers, maybe transitioning off or out of the FDA, and then a different set of reviewers with a different perspective coming in. That does make me hopeful that this will be an isolated case of just regulatory unpredictability rather than a sort of raising of the bar, but it remains to be seen.